The clinical use of prostaglandin derivatives, primarily for gynecological purposes was made possible by the experiments of N. Winquist et al. [Lancet, 889, 1970], and since that time considerable research activity has been going on in this field all over the world including Hungary [Orvosi Hetilap 113, 919-927 (1972); Magyar Noorvosok Lapja 37, 97-103 (1974)]. Prostaglandin F.sub.2.alpha. is generally administered as an injectable solution, for example for interruption of pregnancy, dilation of os uteri and inducing labor. An injectable solution suitable for these purposes is for example disclosed in the Hungarian Patent Specification No. 171,997.
Since the intra-uteral, intraamnial or intravenous administration of the injectable preparations has to be carried out with extra care and skilfulness, there is a long standing demand for other formulations, which can be handled and administered in a more simple way.
It is also known that the oral preparations provide the desired effect only in considerably high doses, and their administration is generally accompanied by an unreasonably large number of side effects.
In gynecology vaginal tablets and semisolid formulations have been used for a long time for local administration. Due to physiological and anatomical reasons, however, such prostaglandin preparations can only restrictedly be used in gynecology and considerable overdoses are required to obtain the desired therapeutic effect. In addition, the use of such preparations is accompanied by numerous uncertanties.
It thus is desirable to prepare and administer cervical or sublingual tablets, from which the active ingredient is liberated at a constant rate, at the locus of treatment. By the processes known in the art prostaglandins could, however, not be formulated into such tablets, primarily because of their well-known instability. The cervical or sublingual tablets, prepared by conventional techniques rapidly lose their active ingredient content during storage, as is shown in Table 1. The tablet tested contained 2.5 mg. of PGF.sub.2.alpha., 24.5 mg. of lactose and 1 mg. of stearin.
TABLE 1 ______________________________________ Storage temperature [.degree.C.] 0 30 40 50 60 Active ingredient content after 30 days 100% 90.3% 85.7% 67.0% 37.2% ______________________________________
Tablets containing mannite or sorbite instead of lactose, and liquid paraffin instead of stearin are just as unstable.
It is known [Hungarian Patent Specification No. 171,997] that the stability of prostaglandin-containing injection preparations can be increased by the addition of alkali metal acetates to a large extent. This method, however, has not led to an increase in stability of prostaglandin-containing tablets.